• Environmental Analysis Health and Toxicology
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• 제19권3호
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• pp.321-326
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• 2004

The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.338-351
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• 2003

UV radiation is the most dangerous stress factor among permanent environmental impacts on human skin. Consequences of UV exposure are aberrant tissue architecture, alterations in skin cells including functional changes. Nowadays new kinds of outdoor leisure-time activities and changing environmental conditions make the question of sun protection more important than ever. It is necessary to recognize that self-confident consumers do not consider to change their way of life, they demand modern solutions on the basis of new scientific developments. In the past one fundamental principle of cosmetics was the use of physical and organic filter systems against damaging UV-rays. Today new research results demonstrate that natural protecting cell mechanisms can be activated. Suitable biological actives strongly support the protection function not from the surface but from the inside of the cell. A soy seed preparation (SSP) was proven to stimulate natural skin protective functions. The major functions are an increased energy level and the prevention of DNA damage. These functions can I be defined as biological UV protection. The tumor suppressor protein p53 plays a key role in the regulation of DNA repair. p53 must be transferred into the phosphorylated form to work as transcription factor for genes which are regulating the cell cycle or organizing DNA repair. A pretreatment with SSP increases the phosphorylation rate of p53 of chronically UV-irradiated human keratinocytes significantly. According to the same test procedure SSP induces a dramatic increase in the expression of the tumor suppressor protein p14$^{ARF}$ that is supporting the p53 activity by blocking the antagonist of p53, the oncoprotein Mdm2. Mdm2, a ubiquitin E3-ligase, downregulates p53 and at the same time it prevents phosphorylation of p53. The positive influence of the tumor suppressor proteins explains the stimulation of DNA repair and prevention of sunburn cell formation by SSP, which was proven in cell culture experiments. In vivo the increased skin tolerance against UV irradiation by SSP could be confirmed too. We have assumed, that an increased repair potential provides full cell functionality.y.

• 한국약용작물학회지
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• 제14권2호
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• pp.96-100
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• 2006

Regions of allelic loss on chromosomes in many tumors of human and some experimental animals are generally considered to harbor tumor-suppressor genes involved in tumorigenesis. Allelotype analyses have greatly improved our under-standing of the molecular mechanism of radiation lymphomagenesis. Previously, we and others found frequent loss of heterozygosity (LOH) on chromosomes 4, 11, 12, 16 and 19 in radiation-induced lymphomas from several $F_1$, hybrid mice. To examine possible contributions of individual tumor-suppressor genes to tumorigenesis in p53 heterozygous deficiency, we investigated the genome-wide distribution and status of LOH in radiation-induced lymphomas from $F_1$ mice with different p53 status. In this study, we found frequent LOH (more than 20%) on chromosomes 4 and 12 and on chromosomes 11, 12, 16 and 19 in radiation-induced lymphomas from $(STS/A{\times}MSM/Ms)F_1$ mice and $(STS/A{\times}MSM/Ms)F_1-p53^{KO/+}$ mice, respectively. Low incidences of LOH (10-20%) were also observed on chromosomes 11 in mice with wild-type p53, and chromosomes 1, 2, 9, 17 and X in p53 heterozygous-deficient mice. The frequency of LOH on chromosomes 9 and 11 increased in the $(STS/A{\times}MSM/Ms)F_1-p53^{KO/+}$ mice. Preferential losses of the STS-derived allele on chromosome 9 and wild-type p53 allele on chromosome 11 were also found in the p53 heterozygous-deficient mice. Thus, the putative tumor-suppressor gene regions responsible for lymphomagenesis might considerably differ due to the p53 status.

• BMB Reports
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• 제56권10호
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• pp.557-562
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• 2023

Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

• 한국임상수의학회지
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• 제19권2호
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• pp.195-198
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• 2002

개에서 자연적으로 발생한 12예의 종양에 대해, 종양 억제 유전자 p53의 변이와의 관계를 확인해 보았다. 종양조직에서 일반적인 방법으로 DNA를 추출하여, PCR 기법으로 p53을 증폭하여 염기서열을 확인한 결과, 개의 유선암종 예에서 exon 8의 codon 285에서 CCT $\longrightarrow$ TCT (proline $\longrightarrow$ serine)로 점변이 된 것이 확인되었다. 또한 악성 비만세포 종양 예에서도 exon 8의 codon 249에서 AGT $\longrightarrow$AGC로 점변이 된 것이 확인되었으나 silent point mutation (serine)으로 판명되었다. 이상의 결과를 토대로 개의 유선암종과 악성 비만세포 종양에서 종양억제 유전자 p53의 변이가 확인되었으며, 이는 종양의 형성과 관련된 p53의 역할이나 종양의 치료 및 예후 판정에 p53 을 활용하는 연구의 초석이 되리라 사료되며, 차후 이 유전자에 대한 광범위한 연구가 지속되어야 하리라 생각된다.

• 대한화학회지
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• 제48권1호
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• pp.33-38
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• 2004

두경부 편평 세포암종(HNSCC: head and neck squamous cell carcinoma) 의 발생과 관련하여 p53 종양 억제 유전자 (tumor suppressor gene) 의 돌연변이는 높은 비율로 나타나는 것으로 보고 되고 있다. 단국대학교 병원에서 두경부 종양으로 진단 받고 수술 받은 환자의 조직 50개를 대상으로 p53 종양 억제 유전자의 exon 5-8 까지의 영역에서 DNA를 추출하여 PCR-SSCP(polymerase chain reaction single strand conformational polymorphism) 방법과 DHPLC(denaturing high performance liquid chromatography) 방법으로 p53체세포 돌연변이(somatic mutation)를 비교 분석하였다. 그 결과 SSCP 분석 방법은 16개(32%), DHPLC 분석 방법은 17개(34%) 를 검출하였고 그 중 SSCP와 DHPLC 분석 방법 모두 exon 8번에서 결실(deletion) 형태의 돌연변이를 확인하였으며 최종적으로 자동 염기 서열 분석기(automatic DNA sequencer) 를 통하여 모든 돌연변이를 확인하였다. DHPLC 분석방법이 SSCP 방법보다 분석 시간이나 노력이 덜 소모되며 보다 더 정확한 돌연변이 검출 방법임을 확인하였다.

• Molecules and Cells
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• 제43권1호
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• pp.23-33
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• 2020

NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB-inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the TP53 gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.

• IMMUNE NETWORK
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• 제1권2호
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• pp.151-161
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• 2001

Background: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost. In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. Method: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. Results: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. Conclusion: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.

• BMB Reports
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• 제48권8호
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• pp.454-460
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• 2015

Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]

• Journal of Gastric Cancer
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• 제3권4호
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• pp.214-220
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• 2003

Purpose: The aim of this study was to investigate the frequency of loss of heterozygosity and the microsatellite instability at multiple tumor suppressor gene loci in gastric adenocarcinomas. Materials and Methods: Loss of heterozygosity and the microsatellite instability at several tumor suppressor gene loci were analyzed in 29 primary gastric carcinomas by using microdissection and the polymerase chain reaction. Results: Twenty-three ($79\%$) of the 29 cases demonstrated loss of heterozygosity at one or more loci. The frequency of loss of heterozygosity at the p53 locus was the highest ($63\%$) and those at the VHL, APC, p16, Rb, MEN1, BRCA1, DPC4, 3p21, and 16p13 region were $41\%,\;36\%,\;19\%,\;29\%,\;33\%,\;26\%,\;21\%,\;32\%,\;and\;11\%$, respectively. Compared with histological type, loss of heterozygosity was more common in diffuse-type gastric cancer (P<0.01). Interestingly, 9 of 10 tumors with allelic deletion at the p53 locus showed loss of heterozygosity at other tumor suppressor gene loci. The microsatellite instability was also detected in 6 ($20\%$) of the 29 cases at one or more loci. Conclusion: These data suggest that frequent loss of heterozygosity and the microsatellite instability at multiple tumor suppressor genes might be required for the development and the progression of gastric carcinomas and that p53 allelic loss may be the most frequent event in the development of gastric carcinomas.